In the United States, there are approximately three million patients with atrial fibrillation (AF), and this number is expected to increase to five million by 2040. AF is an irregular sinus rhythm and atrial dysrhythmia, which results in a rapid, irregular, and unsynchronized contraction of the atrium. In AF, blood is not washed from the left atrial appendage and it stagnates and tends to clot inside the heart. However, these clots are prone to leaving the heart and embolizing to different organs in the body. For example, it has been observed that the clots frequently leave the heart and enter the cerebral vessels, resulting in an embolic stroke. Indeed, patients with AF are at a significantly increased risk of stroke, and it is estimated that patients with AF have, on average, 5 to 6 times greater probability of having a stroke (5-15% annualized risk of stroke) and 18 times greater probability of having an embolic event. This risk of stroke with AF only increases with age, with up to 30% of all strokes in elderly patients occurring due to AF, and with, overall, at least 100,000 strokes per year being attributed to AF in the United States alone.
Medical and ablation therapies have been used to attempt to eliminate AF, but most patients continue to remain in AF after therapy. In this regard, current treatment of AF often includes anticoagulation therapy with warfarin, which has been reported to reduce the risk of stroke by 62%, but requires close monitoring to prevent bleeding complications that may otherwise result in mortality. In fact, even with close attention to warfarin dosing, life-threatening bleeding complications, intracerebral bleeding, or death still occurs in 1-2.5% of these patients every year, with the highest risk of warfarin complications being in elderly patients, who are also at the highest risk of stroke due to AF. Due to this risk, it is estimated that 40% to 65% of elderly patients with AF and at an increased risk of stroke are not receiving anticoagulant therapy with warfarin. However, it has further been estimated that 35% of patients with AF who are not treated with anticoagulants will likely have a stroke during their lifetime.
Antiplatelet therapy with aspirin has been proposed as a possible alternative to warfarin therapy, but to date has not proven to be very effective. Similarly, combination therapy with aspirin and clopidogrel has also not proven to be as effective in preventing clot formation as warfarin. New pharmaceutical agents aimed at factor Xa and thrombin inhibition anticoagulant agents, such as Pradaxa® (Boehringer Ingelheim Pharma GmbH & Co. KG; dabigatran etexilate) have provided similar reductions in stroke rates and less monitoring when compared to warfarin. Nevertheless, many of these agents, including Pradaxa® are contraindicated for patients over 75, have been shown to still result in bleeding complications, and still require compliance from elderly patients who often forget to take their oral medications.
To overcome these limitations of pharmaceutical agent-based therapies for treating AF, catheter-based left atrial appendage occluder devices, such as AMPLATZER® (AGA Medical Corporation), PLAATO® (EV3 Inc.), and WATCHMAN® (Atritech, Inc.), as well as other devices such as the TIGERPAW® system (LAAx, Inc.) and ATRICLIP® (AtriCure, Inc.), have recently been developed. Initial reports regarding the use of these device-based therapies to block the left atrial appendage have provided good results, and have shown that the devices can reduce hemorrhagic stroke as compared to warfarin therapy. However, recent clinical trials with these devices have also shown an associated increase in ischemic stroke, which is in addition to the fact that the implantation of the devices requires a delivery catheter to puncture the atrial septum as well as barbs for anchoring the devices, both of which can lead to several complications including puncturing of the left atrium. Moreover, these current left atrial appendage closure devices are not always completely effective in sealing off the left atrial appendage due to patient-to-patient variability in left atrial appendage sizes, thus leading to embolic clots. Further, it is also possible that any foreign material in the left atrial appendage may also cause thrombus formation. Accordingly, an atrial appendage closure device that avoids the adverse events common with current catheter-based left atrial appendage occluder devices or common with current pharmaceutical therapies would be both highly-desirable and beneficial.